Enhancing routine HIV and STI testing among young men who have sex with men: primary outcomes of the get connected clinical randomized trial (ATN 139).

BACKGROUND: Regular HIV and STI testing remain a cornerstone of comprehensive sexual health care. In this study, we examine the efficacy of Get Connected, a WebApp that combines test locators with personalized educational resources, in motivating young men who have sex with men (YMSM) to undergo regular HIV and STI testing. METHODS: Participants were randomly placed in one of two conditions. The first condition included the full version of GC (GC-PLUS), which included content tailored to users' psychosocial characteristics (e.g., age, race/ethnicity, relationship status, HIV/STI testing history). The second condition served as our attention-control and only included the testing locator (GC-TLO) for HIV/STI testing services. Participants were recruited from three cities (Houston, Philadelphia, and Atlanta) characterized by high HIV incidence. Assessments were collected at 1, 3-, 6-, 9- and 12-month follow-ups. RESULTS: Both versions of GC were acceptable and efficacious in increasing routine HIV and STI testing over a 12-month period. 40% of the sample reported testing at least twice, with no main effects observed across the two intervention arms (OR = 1.11; 95% CI: 0.69, 1.80), p =.66). Greater intervention effects were observed among YMSM who engaged more frequently with the intervention, with regional differences observed. CONCLUSIONS: Our findings underscore the need to cater to the diverse needs of YMSM through multilevel approaches. Broadly, mHealth HIV/STI testing interventions, such as Get Connected, would benefit from matching technologies to the local context to have the greatest impact. TRIAL REGISTRATION: This study is registered on ClinicalTrials.gov (NCT03132415).

NDVI changes in the Arctic: Functional significance in the moist acidic tundra of Northern Alaska.

The Normalized Difference Vegetation Index (NDVI), derived from reflected visible and infrared radiation, has been critical to understanding change across the Arctic, but relatively few ground truthing efforts have directly linked NDVI to structural and functional properties of Arctic tundra ecosystems. To improve the interpretation of changing NDVI within moist acidic tundra (MAT), a common Arctic ecosystem, we coupled measurements of NDVI, vegetation structure, and CO2 flux in seventy MAT plots, chosen to represent the full range of typical MAT vegetation conditions, over two growing seasons. Light-saturated photosynthesis, ecosystem respiration, and net ecosystem CO2 exchange were well predicted by NDVI, but not by vertically-projected leaf area, our nondestructive proxy for leaf area index (LAI). Further, our data indicate that NDVI in this ecosystem is driven primarily by the biochemical properties of the canopy leaves of the dominant plant functional types, rather than purely the amount of leaf area; NDVI was more strongly correlated with top cover and repeated cover of deciduous shrubs than other plant functional types, a finding supported by our data from separate "monotypic" plots. In these pure stands of a plant functional type, deciduous shrubs exhibited higher NDVI than any other plant functional type. Likewise, leaves from the two most common deciduous shrubs, Betula nana and Salix pulchra, exhibited higher leaf-level NDVI than those from the codominant graminoid, Eriophorum vaginatum. Our findings suggest that recent increases in NDVI in MAT in the North American Arctic are largely driven by expanding deciduous shrub canopies, with substantial implications for MAT ecosystem function, especially net carbon uptake.

The Relationship Between Sexual Behavior Stigma and Depression Among Men Who have Sex with Men and Transgender Women in Kigali, Rwanda: a Cross-sectional Study.

To evaluate the role of sexual behavior stigma as a determinant of depressive symptoms among men who have sex with men (MSM) and transgender women (TGW) in Kigali, Rwanda. MSM/TGW aged ≥18 years were recruited using respondent-driven sampling (RDS) between March-August, 2018. Mental health was assessed using the Patient Health Questionnaire (PHQ-9). Sexual behavior stigma from friends and family, healthcare workers, and community members was assessed using a validated instrument. Multinomial logistic regression models were used to determine the association between sexual behavior stigma and depressive symptoms and depression. Secondary analyses further compared depression and depressive symptoms among MSM and TGW. Among the 736 participants included, 14% (106/736) identified as TGW. Depression 8.9% (RDS-adjusted, 7.6%; 95% CI, 4.6-10.6) and mild/moderate symptoms of depression 26.4% (RDS-adjusted, 24.1%; 95% CI, 19.4-28.7) were common and higher among TGW compared to MSM (p < 0.001). Anticipated (41%), perceived (36%), and enacted (45%) stigmas were highly prevalent, and were also significantly higher among TGW (p < 0.001). In multivariable RDS-adjusted analysis, anticipated (relative risk ratio (RRR), 1.88; 95% CI, 1.11-3.19) and perceived (RRR, 2.06; 95% CI, 1.12-3.79) stigmas were associated with a higher prevalence of depressive symptoms. Anticipated (RRR, 4.78; 95% CI, 1.74-13.13) and enacted (RRR, 3.09; 95% CI, 1.61-5.93) stigmas were also associated with a higher prevalence of depression. In secondary analyses, the significant differences between MSM and TGW were lost after adjusting for stigma. These data demonstrate a high burden of depressive symptoms and depression among MSM/TGW in Kigali. Conceptually, stigma is a likely antecedent of mental health stress among MSM and TGW suggesting the potential utility of scaling up stigma mitigation interventions to improve the quality of life and mental health outcomes among sexual and gender minority communities in Rwanda.

Dysregulation of synaptic and developmental transcriptomic/proteomic profiles upon depletion of MUNC18-1.

Absence of presynaptic protein MUNC18-1 (gene: Stxbp1) leads to neuronal cell death at an immature stage before synapse formation. Here, we performed transcriptomic and proteomic profiling of immature Stxbp1 knockout (KO) cells to discover which cellular processes depend on MUNC18-1. Hippocampi of Stxbp1 KO mice showed cell-type specific dysregulation of 2123 transcripts primarily related to synaptic transmission and immune response. To further investigate direct, neuron-specific effects of MUNC18-1 depletion, a proteomic screen was performed on murine neuronal cultures at two developmental timepoints prior to onset of neuron degeneration. 399 proteins were differentially expressed, which were primarily involved in synaptic function (especially synaptic vesicle exocytosis) and neuron development. We further show that many of the downregulated proteins upon loss of MUNC18-1 are normally upregulated during this developmental stage. Thus, absence of MUNC18-1 extensively dysregulates the transcriptome and proteome, primarily affecting synaptic and developmental profiles. Lack of synaptic activity is unlikely to underlie these effects, as the changes were observed in immature neurons without functional synapses, and minimal overlap was found to activity-dependent proteins. We hypothesize that presence of MUNC18-1 is essential to advance neuron development, serving as a 'checkpoint' for neurons to initiate cell death in its absence.Significance StatementPresynaptic protein MUNC18-1 is essential for neuronal functioning. Pathogenic variants in its gene, STXBP1, are among the most common found in patients with developmental delay and epilepsy. To discern the pathogenesis in these patients, a thorough understanding of MUNC18-1's function in neurons is required. Here, we show that loss of MUNC18-1 results in extensive dysregulation of synaptic and developmental proteins in immature neurons before synapse formation. Many of the downregulated proteins are normally upregulated during this developmental stage. This indicates that MUNC18-1 is a critical regulator of neuronal development, which could play an important role in the pathogenesis of STXBP1 variant carriers.

Developing priorities for quality improvement in acute medicine using a modified Delphi method A consensus process hosted by the Society for Acute Medicine Quality Improvement Committee (SAM-QI).

INTRODUCTION: The SAM Quality Improvement Committee (SAM-QI), set up in 2016, has worked over the last year to determine the priority Acute Medicine QI topics. They have also discussed and put forward proposals to improve QI training for Acute Medicine professionals. METHODS: A modified Delphi process was completed over four rounds to determine priority QI topics. Online meetings were also used to develop proposals for QI training. RESULTS: Same Day Emergency Care (SDEC) was chosen as the priority topic for QI work within Acute Medicine. CONCLUSION: The SAM-QI group settled on SDEC being the priority topic for Acute Medicine QI development. Throughout the Delphi process SAM-QI has also developed proposals for QI training that will help Acute Medicine professionals deliver coordinated meaningful improvements in care.

Technological readiness and implementation of genomic-driven precision medicine for complex diseases.

The fields of human genetics and genomics have generated considerable knowledge about the mechanistic basis of many diseases. Genomic approaches to diagnosis, prognostication, prevention and treatment - genomic-driven precision medicine (GDPM) - may help optimize medical practice. Here, we provide a comprehensive review of GDPM of complex diseases across major medical specialties. We focus on technological readiness: how rapidly a test can be implemented into health care. Although these areas of medicine are diverse, key similarities exist across almost all areas. Many medical areas have, within their standards of care, at least one GDPM test for a genetic variant of strong effect that aids the identification/diagnosis of a more homogeneous subset within a larger disease group or identifies a subset with different therapeutic requirements. However, for almost all complex diseases, the majority of patients do not carry established single-gene mutations with large effects. Thus, research is underway that seeks to determine the polygenic basis of many complex diseases. Nevertheless, most complex diseases are caused by the interplay of genetic, behavioural and environmental risk factors, which will likely necessitate models for prediction and diagnosis that incorporate genetic and non-genetic data.

Quality: What does it mean in Acute Medicine and how do we measure it?

Acute Medicine is a specialty that is not defined by a single organ system and sits at the interface between primary and secondary care. In order to document improvements in the quality of care delivered a system of metrics is required. A number of frameworks for measurements exist to quantify quality of care at the level of patients, teams and organisations, such as measures of population health, patient satisfaction and cost per patient. Measures can capture whether care is safe, effective, patient-centred, timely, efficient and equitable. Measurement in Acute Medicine is challenged by the often-transient nature of the contact between Acute Medicine clinicians and patients, the lack of diagnostic labels, a low degree of standardisation and difficulties in capturing the patient experience in the context. In a time of increasing ecological and financial constraints, reflecting about the most appropriate metrics to document the impact of Acute Medicine is required.

Inactivation of TMEM106A promotes lipopolysaccharide-induced inflammation via the MAPK and NF-κB signaling pathways in macrophages.

Pattern recognition receptors, such as Toll-like receptors (TLRs), play an important role in the host defense against invading microbial pathogens. Their activation must be precisely regulated, as inappropriate activation or overactivation of TLR signaling pathways may result in inflammatory disorders, such as septic shock or autoimmune diseases. TMEM106A is a type II transmembrane protein constitutively expressed in macrophages. Our current study demonstrated that TMEM106A levels were increased in macrophages upon lipopolysaccharide (LPS) stimulation, as well as in the peripheral monocytes of patients with sepsis. Tmem106a knockout mice were more sensitive to lipopolysaccharide (LPS)-induced septic shock than wild-type mice. Further experiments indicated that Tmem106a ablation enhanced the expression of CD80, CD86 and major histocompatibility complex (MHC)-II in mouse macrophages upon LPS stimulation, accompanied with up-regulation of tumor necrosis factor (TNF)-α, interleukin (IL)-6, interferon (IFN)-ß and inducible nitric oxide synthase (iNOS), indicating the activation of macrophages and polarization towards the M1 inflammatory phenotype. Moreover, elevated mitogen-activated protein kinase (MAPK) and nuclear factor kappa B (NF-κB) signaling were found to be involved in the LPS-induced inflammatory response in Tmem106a-/- macrophages. However, this effect was largely abrogated by macrophage deletion in Tmem106a-/- mice. Therefore, deficiency of Tmem106a in macrophages may enhance the M1 polarization in mice, resulting in inflammation. This suggests that TMEM106A plays an important regulatory role in maintaining macrophage homeostasis.

Missed Prevention Opportunities: Why Young, Black MSM with Recent HIV Diagnosis did not Access HIV Pre-exposure Prophylaxis Services.

In the United States, HIV infection rate inequities persist, with new infections highest among young, Black men who have sex with men (YBMSM) in the South. We conducted 23 in-depth interviews with YBMSM newly diagnosed with HIV to explore awareness of and barriers to uptake of HIV pre-exposure prophylaxis (PrEP). Participants were recruited from two university-based HIV Clinics in Alabama and were: (1) 16-29 years of age, (2) diagnosed with HIV within the prior 365 days, (3) Black race, (4) self-identified as a cis-gender male reporting sex with men AND (5) did not report prior PrEP use. Interview guides were grounded in Anderson's Behavioral Healthcare Utilization Model (ABM), with embedded constructs from the situated Information, Motivation and Behavioral Skills theoretical framework. Coding was conducted by three independent coders using thematic analysis methods. Participants (N = 23) median age was 24, more than two-thirds reported annual incomes less than $15,000 and the majority (84%) identified as gay. Major themes that emerged as barriers to accessing PrEP included low prioritization and interests in using PrEP; low perceived HIV risk due to feelings of invincibility and trust in sex partners; lack of information about accessing PrEP; negative beliefs around PrEP; and the suggestion to change PrEP messaging from only targeting YBMSM. These findings indicate that there are important missed opportunities for HIV prevention with PrEP among YBMSM in the South. In these high-risk young men, tailored interventions are needed to better inform and frame perceptions around risk, knowledge, access and prioritization of PrEP.

En Estados Unidos, desigualdades en la tasa de infección por VIH persisten, y en el sur del pais, la tasa de nuevas infecciones hombres jóvenes Afro-americanos que tienen sexo con hombres son más altas. Realizamos veintitrés entrevistas en profundidad con YBMSM recién diagnosticado con VIH para explorar la conciencia y las barreras para la adopción de la profilaxis previa a la exposición al VIH (PrEP). Los participantes fueron reclutados de dos clínicas de VIH en centros medicos academicos en el estado de Alabama con los siguientes criterios: 1) 16-29 años de edad, 2) diagnostico VIH dentro de los 365 días, 3) raza afro-americana, 4) autoidentificados como un género cis-hombres que tienen sexo con hombres, y 5) no informaron el uso previo de PrEP. Las guías de la entrevista se basaron en el Modelo conductual de utilización de la salud (ABM) de Anderson, con construcciones integradas del marco teórico de Información, motivación y habilidades conductuales. Tres codificadores independientes codificaron utilizando métodos de análisis temáticos. La edad mediana de los participantes (N = 23) era de 24 años, más de dos tercios informaron ingresos anuales de menos de $15,000 (USD) y la mayoría (84%) se identificó como gay. Los temas principales que surgieron como barreras para acceder a PrEP incluyeron una baja priorización e interes en su; bajo riesgo percibido de VIH debido a sentimientos de invencibilidad y confianza en las parejas sexuales; falta de información sobre el acceso a PrEP; creencias negativas sobre PrEP; y la sugerencia de enfocar los mensajes sobre PreP no solo ha jovenes afro-americanos que tienen sexo con hombres. Estos hallazgos indican que hay importantes oportunidades perdidas para la prevención del VIH con PrEP entre esto jovenes en el Sur de EEUU. En estos hombres jóvenes de alto riesgo, se necesitan intervenciones personalizadas para mejor informar y enmarcar las percepciones sobre el riesgo, el conocimiento, el acceso y la priorización de PrEP.

Herd-level factors associated with detection of calves persistently infected with bovine viral diarrhoea virus (BVDV) in Irish cattle herds with negative herd status (NHS) during 2017.

A compulsory national BVD eradication programme commenced in Ireland in 2013. Since then considerable progress has been made, with the animal-level prevalence of calves born persistently infected (PI) falling from 0.67 % in 2013 to 0.06 % in 2018. The herd-level prevalence fell from 11.3 % in 2013 to 1.1 % in 2018. In the Irish programme, herds in which all animals have a known negative status and which have not contained any PI animals for 12 months or more are assigned a negative herd status (NHS). While considerable progress towards eradication has been made, PI calves have been identified in a small proportion of herds that had previously been assigned NHS. Given this context, a case-control study was conducted to investigate potential risk factors associated with loss of NHS in 2017. 546 herds which had NHS on 1 January 2017 and lost that status during 2017 (case herds) were matched with 2191 herds (control herds) that retained their NHS status throughout 2017. Previous history of BVD infection, herd size, herd expansion, the purchase of cattle including potential Trojan cattle and the density of BVD infection within 10 km of the herd emerged as significant factors in a multivariable logistic regression model. This work adds to the evidence base in support of the BVD eradication programme, particularly establishing why BVD re-emerged in herds which had been free of BVD for at least the previous 12 months prior to the identification of a BVD positive calf. This information will be especially important in the context of identifying herds which may be more likely to contain BVD positive animals once the programme moves to herd-based serology status for trading purposes in the post-eradication phase.

Stitching the synapse: Cross-linking mass spectrometry into resolving synaptic protein interactions.

Synaptic transmission is the predominant form of communication in the brain. It requires functionally specialized molecular machineries constituted by thousands of interacting synaptic proteins. Here, we made use of recent advances in cross-linking mass spectrometry (XL-MS) in combination with biochemical and computational approaches to reveal the architecture and assembly of synaptic protein complexes from mouse brain hippocampus and cerebellum. We obtained 11,999 unique lysine-lysine cross-links, comprising connections within and between 2362 proteins. This extensive collection was the basis to identify novel protein partners, to model protein conformational dynamics, and to delineate within and between protein interactions of main synaptic constituents, such as Camk2, the AMPA-type glutamate receptor, and associated proteins. Using XL-MS, we generated a protein interaction resource that we made easily accessible via a web-based platform (http://xlink.cncr.nl) to provide new entries into exploration of all protein interactions identified.

Exploring factors associated with health disparities in asthma and poorly controlled asthma among school-aged children in the U.S.

Objective: Certain populations suffer disproportionately from asthma and asthma morbidity. The objective was to provide a national descriptive profile of asthma control and treatment patterns among school-aged children (SAC: aged 6-17) in the U.S. Methods: This was a cross-sectional analysis using the nationally representative 2007-2014 Medical Expenditure Panel Survey. Among SAC with asthma, indicators of poor control included: exacerbation/asthma attack; >3 canisters short-acting beta agonist (SABA)/3 months; and asthma-specific Emergency Department or inpatient visits (ED/IP). Results: Non-Hispanic black, non-Hispanic multiple races, Puerto Rican, obese, Medicaid, poor, ≥2 non-asthma chronic comorbidities (CC), and family average CC ≥ 2 were associated with higher odds of having asthma. The following had significantly higher odds ratios (OR) of excessive SABA use compared to non-Hispanic whites [OR; CI; p < 0.05]: Puerto Rican (3.8; 2.1-6.9), Mexican (3.6; 2.0-6.4), Central/South American (3.0; 1.2-7.7), Hispanic-other (3.1; 1.1-9.0), non-Hispanic black (2.5; 1.6-3.9), and non-Hispanic Asian (4.0; 1.7-9.2). SABA OR were also significant for Spanish spoken at home (2.5; 1.6-3.8), obese (2.1; 1.3-3.3), Medicaid (2.9; 2.0-4.1), no medical insurance (2.1; 1.1-4.1), no prescription insurance (2.5; 1.8-3.5), poor (2.8; 1.7-4.7), CC ≥ 2 (2.1; 1.6-2.8), parent-without high-school degree (2.5; 1.8-3.6), parent-SF-12 Physical Component Scale <50 (1.6; 1.2-2.1) and Mental Component Scale <50 (1.5; 1.1-2.0). Significant differences also existed across subgroups for ED/IP visits. Conclusions: There are disparities in asthma control and prevalence among certain populations in the U.S. These results provide national data on disparities in several indicators of poor asthma control beyond the standard race/ethnicity groupings.

Survey of surgical training and experience of associate clinicians compared with medical officers to understand task-shifting in a low-income country.

Background: A workforce crisis exists in global surgery. One solution is task-shifting, the delegation of surgical tasks to non-physician clinicians or associate clinicians (ACs). Although several studies have shown that ACs have similar postoperative outcomes compared with physicians, little is known about their surgical training. This study aimed to characterize the surgical training and experience of ACs compared with medical officers (MOs) in Tanzania. Methods: All surgical care providers in Pwani Region, Tanzania, were surveyed. Participants reported demographic data, years of training, and procedures assisted and performed during training. They answered open-ended questions about training and post-training surgical experience. The median number of training cases for commonly performed procedures was compared by cadre using Wilcoxon rank sum and Student's t tests. The researchers performed modified content analysis of participants' answers to open-ended questions on training needs and experiences. Results: A total of 21 ACs and 12 MOs participated. ACs reported higher exposure than MOs to similar procedures before their first independent operation (median 40 versus 17 cases respectively; P = 0·031). There was no difference between ACs and MOs in total training surgical volume across common procedures (median 150 versus 171 cases; P = 0·995). Both groups reflected similarly upon their training. Each cadre relied on the other for support and teaching, but noted insufficient specialist supervision during training and independent practice. Conclusions: ACs report similar training and operative experience compared with their physician colleagues in Tanzania.

Antecedentes: La falta de cirujanos en determinadas áreas geográficas es flagrante. Una posible solución es el intercambio de tareas, es decir, la delegación de tareas quirúrgicas en personal sanitario no médico o en clínicos asociados (associate clinicians, AC). Si bien varios estudios han demostrado que los AC obtienen resultados postoperatorios similares a los de los médicos, hay poco información acerca de su entrenamiento quirúrgico. Este estudio tuvo como objetivo caracterizar la capacitación quirúrgica y la experiencia de los AC en comparación con los médicos titulados (medical officer, MO) en Tanzania. Métodos: En este estudio, se encuestaron todos los proveedores de atención quirúrgica de la Región de Pwani, Tanzania. Los participantes proporcionaron datos demográficos, años de entrenamiento y número y tipo de procedimientos realizados y a los que se había asistido durante el periodo de capacitación. Además, respondieron a preguntas abiertas sobre el entrenamiento y su experiencia quirúrgica posterior al entrenamiento. Se comparó la mediana del número de procedimientos más realizados por cada grupo mediante la suma de rangos de Wilcoxon y la prueba de la t de Student. Los investigadores realizaron un análisis del contenido de las respuestas a las preguntas abiertas sobre las necesidades y la experiencia durante la etapa de entrenamiento. Resultados: En el estudio participaron 21 ACs y 12 MOs. Los CA estuvieron expuestos a un mayor número procedimientos del mismo tipo antes de efectuar su primera operación de forma independiente en comparación con los OM (40 versus 17 casos, P = 0,031). No hubo diferencias en el volumen operatorio total de los procedimientos comunes entre los AC y los MO (150 versus 171 casos, P = 0,995). Las opiniones de los dos grupos sobre el entrenamiento fueron similares. Los dos grupos se dieron soporte entre ellos, pero quedó patente que la supervisión por parte de un especialista durante el entrenamiento y la práctica independiente era insuficiente. Conclusiones: En Tanzania, los asociados clínicos tienen entrenamientos y experiencias quirúrgicas similares a las de sus colegas médicos.

Visual demonstration of aliasing in planar nuclear medicine imaging: The importance of correct collimator selection by nuclear medicine practitioners.

Aliasing artefact is an imaging distortion phenomenon experienced in a wide variety of medical imaging modalities. This case report illustrates its occurrence during planar gamma camera nuclear medicine imaging under non-clinical conditions using experimental incorrect selection of collimators. In accordance with provision of an optimal service, nuclear medicine practitioners are recommended to have sufficient technical expertise along with knowledge of gamma camera operation. The purpose, construction and interaction of collimators used during planar imaging are presented herein with specific regards to the aliasing phenomenon. Furthermore, this case report recommends the careful planning of worklists to avoid frequent collimator changes to reduce the risk of human error.

Unraveling the genetic architecture of major depressive disorder: merits and pitfalls of the approaches used in genome-wide association studies.

To identify genetic risk loci for major depressive disorder (MDD), two broad study design approaches have been applied: (1) to maximize sample size by combining data from different phenotype assessment modalities (e.g. clinical interview, self-report questionnaires) and (2) to reduce phenotypic heterogeneity through selecting more homogenous MDD subtypes. The value of these strategies has been debated. In this review, we summarize the most recent findings of large genomic studies that applied these approaches, and we highlight the merits and pitfalls of both approaches with particular attention to methodological and psychometric issues. We also discuss the results of analyses that investigated the heterogeneity of MDD. We conclude that both study designs are essential for further research. So far, increasing sample size has led to the identification of a relatively high number of genomic loci linked to depression. However, part of the identified variants may be related to a phenotype common to internalizing disorders and related traits. As such, samples containing detailed clinical information are needed to dissect depression heterogeneity and enable the potential identification of variants specific to a more restricted MDD phenotype. A balanced portfolio reconciling both study design approaches is the optimal approach to progress further in unraveling the genetic architecture of depression.

Connecting Youth and Young Adults to Optimize Antiretroviral Therapy Adherence (YouTHrive): Protocol for a Randomized Controlled Trial.

BACKGROUND: Despite intensive efforts to engage people living with HIV in the United States, less than half of the youth aged 13 to 24 years achieve viral suppression. There is a clear and continued need for innovative behavioral programs that support optimizing adherence among young persons with HIV. OBJECTIVE: There are 3 phases of this project. Phase 1 involves conducting focus groups to obtain feedback from youth about an existing technology-based antiretroviral therapy (ART) adherence intervention. Phase 2 will be used to conduct beta testing with youth to refine and finalize the YouTHrive (YT) intervention. Phase 3 is a randomized controlled trial (RCT) to test the efficacy of the YT intervention among youth living with HIV (YLWH). METHODS: In phase 1, we will conduct 6 focus groups with approximately 8 youths (aged 15-19 years) and young adults (aged 20-24 years), each in 3 US cities to obtain (1) feedback from YLWH about the look and feel and content of an existing adult-focused Web-based ART adherence intervention and (2) suggestions for adapting the intervention for YLWH similar to themselves. Phase 2 will involve updating the existing intervention to include features and functionality recommended by YLWH in phase 1; it will conclude with beta testing with 12 participants to gain feedback on the overall design and ensure proper functionality and ease of navigation. For phase 3, we will enroll 300 YLWH in 6 US cities (Atlanta, Chicago, Houston, New York City, Philadelphia, and Tampa) into a 2-arm prospective RCT. Participants will be randomized 1:1 to YT intervention or control group. The randomization sequence will be stratified by city and use random permuted blocks of sizes 2 and 4. Participants randomized to the control condition will view a weekly email newsletter on topics related to HIV, with the exception of ART adherence, for 5 months. Participants randomized to the YT intervention condition will be given access to the YT site for 5 months. Study assessments will occur at enrollment and 5, 8, and 11 months post enrollment. The primary outcome that will be assessed is sustained viral load (VL), defined as the proportion of participants in each study arm who have suppressed VL at both the 5- and 11-month assessment; the secondary outcome that will be assessed is suppressed VL at both the 5- and 11-month assessment between drug-using and nondrug-using participants assigned to the YT intervention arm. RESULTS: Participant recruitment began in May 2017 for phase 1 of the study. The data collection for aim 3 is anticipated to end in April 2020. CONCLUSIONS: The efficacy trial of the YT intervention will help to fill gaps in understanding the efficacy of mobile interventions to improve ART adherence among at-risk populations. TRIAL REGISTRATION: ClinicalTrials.gov NCT03149757; https://clinicaltrials.gov/ct2/show/NCT03149757 (Archived by WebCite at http://www.webcitation.org/73pw57Cf1). INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/11502.

RESTORE-Cognitive functional therapy with or without movement sensor biofeedback versus usual care for chronic, disabling low back pain: study protocol for a randomised controlled trial.

INTRODUCTION: Low back pain (LBP) is the leading cause of disability globally and its costs exceed those of cancer and diabetes combined. Recent evidence suggests that individualised cognitive and movement rehabilitation combined with lifestyle advice (cognitive functional therapy (CFT)) may produce larger and more sustained effects than traditional approaches, and movement sensor biofeedback may enhance outcomes. Therefore, this three-arm randomised controlled trial (RCT) aims to compare the clinical effectiveness and economic efficiency of individualised CFT delivered with or without movement sensor biofeedback, with usual care for patients with chronic, disabling LBP. METHODS AND ANALYSIS: Pragmatic, three-arm, randomised, parallel group, superiority RCT comparing usual care (n=164) with CFT (n=164) and CFT-plus-movement-sensor-biofeedback (n=164). Inclusion criteria include: adults with a current episode of LBP >3 months; sought primary care ≥6 weeks ago for this episode of LBP; average LBP intensity of ≥4 (0-10 scale); at least moderate pain-related interference with work or daily activities. The CFT-only and CFT-plus-movement-sensor-biofeedback participants will receive seven treatment sessions over 12 weeks plus a 'booster' session at 26 weeks. All participants will be assessed at baseline, 3, 6, 13, 26, 40 and 52 weeks. The primary outcome is pain-related physical activity limitation (Roland Morris Disability Questionnaire). Linear mixed models will be used to assess the effect of treatment on physical activity limitation across all time points, with the primary comparison being a formal test of adjusted mean differences between groups at 13 weeks. For the economic (cost-utility) analysis, the primary outcome of clinical effect will be quality-adjusted life years measured across the 12-month follow-up using the EuroQol EQ-5D-5L . ETHICS AND DISSEMINATION: Approved by Curtin University Human Research Ethics Committee (HRE2018-0062, 6 Feb 2018). Study findings will be disseminated through publication in peer-reviewed journals and conference presentations. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trials Registry (ACTRN12618001396213).